Chronic Lymphocytic Leukemia (CLL)

Symptoms, Doctors, Treatments, Advances & More

Chronic lymphocytic leukemia (CLL) is a slow-growing cancer of the blood and bone marrow which produces high levels of abnormal white blood cells (lymphocytes). Unlike normal cells, the abnormal white blood cells in chronic lymphocytic leukemia do not fight infection properly and crowd out red blood cells and platelets, which may result in anemia, infections, and bleeding. While chronic lymphocytic leukemia starts in the bone marrow, over time the disease spreads through the bloodstream to other parts of the body, especially the lymph nodes, as well as the liver and spleen, which then become enlarged. There are two main types of chronic lymphocytic leukemia, one that progresses very slowly (B cell), and one that progresses more quickly (T cell), which is the more serious type. Diagnostic tests can determine if chronic lymphocytic leukemia is the type that progresses slowly by finding the proteins, ZAP-70 and CD38, on the leukemia cells, which can predict a better long-term outcome. Chronic lymphocytic leukemia is the most common type of leukemia in adults, and more often affects individuals who are white, middle-aged, or older, usually over the age of 70, while occurring very rarely in children. In general, chronic lymphocytic leukemia is categorized as asymptomatic (without symptoms), symptomatic, progressive, refractory (resistant to treatment), or recurrent. Chronic lymphocytic leukemia is further categorized by the following stages: Stage 0 – Too many white blood cells (lymphocytes), without any sign or symptom of leukemia. This is a slow-growing stage. Stage I – Too many white blood cells (lymphocytes) and enlarged lymph nodes. Stage II – Too many white blood cells (lymphocytes), enlarged liver, spleen, or lymph nodes. Stage III – Too many white blood cells (lymphocytes), and not enough red blood cells, enlarged liver, spleen, or lymph nodes. Stage IV – Too many white blood cells, and not enough platelets or red blood cells, enlarged liver, spleen, or lymph nodes. The stage of chronic lymphocytic leukemia helps to determine the treatment and outcome (prognosis).

Chronic lymphocytic leukemia is often abbreviated to CLL.

The causes of chronic lymphocytic leukemia are unknown. However, it is known that a genetic mutation in the DNA of the cells that produce blood occurs from the loss of a part of a chromosome (deletion), which, in turn, causes the blood cells to produce abnormal white blood cells (lymphocytes). Some scientists believe that chronic lymphocytic leukemia develops when the B lymphocytes (white blood cells) continue to increase after reacting to an antigen (foreign substance). Since chronic lymphocytic leukemia is more common in North America and Europe than in Asia, most scientists believe that its cause may be genetic. Several risk factors can increase the chances of developing chronic lymphocytic leukemia, such as being white, increased age (90% over age 50), male, having a family history of blood and bone marrow cancers, and having a history of exposure to certain chemicals, such as herbicides and insecticides, as well as the defoliant chemical, Agent Orange, which was used during the Vietnam War, and exposure to radon in the home.

Early stage chronic lymphocytic leukemia may not have any signs of symptoms and may only be discovered via a blood test upon examination for another condition. Later stage chronic lymphocytic leukemia may exhibit the following signs and symptoms: weakness, fatigue, enlarged, painless lymph nodes around the neck, under the arm (axillary), or in the stomach or groin, a feeling of pain or fullness below the ribs, unexplained weight loss, fever, chills, frequent colds, recurrent infections, easy bruising or bleeding, bleeding gums, nosebleeds, flat, pinpoint, red spots under the skin (petechiae), shortness of breath (dyspnea), night sweats, pneumonia, and anemia.

Since chronic lymphocytic leukemia usually progresses slowly, many patients will not need treatment for a significant length of time, sometimes for decades. However, in the case of chronic lymphocytic leukemia that is progressing rapidly, early treatment is needed. Treatments for chronic lymphocytic leukemia may include watchful waiting, radiation therapy, chemotherapy, targeted therapy, immunotherapy (biotherapy or biologics), chemotherapy combined with bone marrow transplant (stem cell transplant), and leukapheresis (cell reduction). Watchful waiting (Stage 0) – Watchful waiting involves observing a patient with early chronic lymphocytic leukemia who is usually without symptoms (asymptomatic) for the appearance of any symptoms or a change in their condition. Radiation therapy – Radiation therapy uses intense, directed X-rays, protons, or other types of radiation to stop cancer cells from growing or to kill cancer cells. Chemotherapy – Chemotherapy (with or without steroids) uses drugs that can be administered either orally or intravenously (systemic chemotherapy; IV). Targeted therapy – Targeted therapy uses drugs that are designed to attack certain characteristics in cancer cells. Types of targeted therapies used to treat chronic lymphocytic leukemia include tyrosine kinase inhibitors (TKIs), BLC2 inhibitor therapy, and monoclonal antibody therapy. Tyrosine kinase inhibitors (TKIs) –Tyrosine kinase inhibitors stop tumors from growing, and include the targeted therapy drugs, ibrutinib, idelalisib, and duvelisib, for the treatment of chronic lymphocytic leukemia. BCL2 inhibitor therapy – BCL2 therapy blocks a protein on leukemia cells, allowing them to become more receptive to anticancer drugs, and includes the drug, Venetoclax, for the treatment of chronic lymphocytic leukemia. Monoclonal antibody therapy – Monoclonal antibody therapy is made from antibodies grown in the laboratory from an immune system cell that can stop cancer cells from growing, stop cancer cells from spreading, or kill cancer cells, and includes the drugs rituximab, ofatumumab, and Obinutuzumab, either alone or in combination with chemotherapy, to treat symptomatic or progressive chronic lymphocytic leukemia. Immunotherapy (Biotherapy or Biologic Therapy) – Immunotherapy uses the patient’s immune system to increase, control, or reset the body’s natural immunity to fight cancer. Types of immunotherapy include immunomodulating agents and CAR T-Cell Therapy. Immunomodulating agents – Immunomodulating agents increase the ability of the body’s T cells (immune cells) to kill leukemia, and include the drug, lenalidomide, which can be used either alone or in combination with rituximab for patients with symptomatic or progressive chronic lymphocytic leukemia. CAR T-Cell Therapy – Car T-cell therapy is a type of immunotherapy that alters T cells, so that they can attack cancer cells. The T cells are first extracted from the patient and altered in a laboratory, and then returned to the patient via infusion. The CAR T cells then increase in the blood, kill the leukemia cells, and are used in the treatment of symptomatic or progressive chronic lymphocytic leukemia. Chemotherapy with Bone Marrow Transplant (Stem Cell Transplant) – This treatment first uses chemotherapy to destroy leukemia cells, and then stem cells extracted from either the blood or bone marrow are returned to the patient via infusion. The new stem cells grow into healthy blood cells. Leukapheresis – This treatment lowers the number of excessive cells in chronic lymphocytic leukemia that may interfere with circulation and can be given before or after chemotherapy. Clinical trials – Some patients may also want to enroll in clinical trials to gain access to new, experimental treatments for chronic lymphocytic leukemia. Treatments for chronic lymphocytic leukemia may include watchful waiting, radiation therapy, chemotherapy, targeted therapy, immunotherapy (biotherapy or biologics), chemotherapy combined with bone marrow transplant (stem cell transplant), and leukapheresis (cell reduction). Green tea extract in pill form is an alternative treatment that has demonstrated some effectiveness for treating early chronic lymphocytic leukemia by killing leukemia cells with its compound EGCG; however, more study is needed.

There are a variety of support groups available for chronic lymphocytic leukemia. CancerCare - https://www.cancercare.org/diagnosis/chronic_lymphocytic_leukemia Cancer Support Community - https://www.cancersupportcommunity.org/chronic-lymphocytic-leukemiasmall-lymphocytic CLL Society - https://cllsociety.org/support-groups/ Leukemia and Lymphoma Society - https://www.lls.org/leukemia/chronic-lymphocytic-leukemia?src1=20032&src2=

While there is no cure for chronic lymphocytic leukemia, patients with this disease can live for many years without experiencing symptoms or having the disease progress too rapidly. Individuals with the slow-growing type of chronic lymphocytic leukemia (B cell) live longer and are often also able to delay treatment longer.

Complications of chronic lymphocytic leukemia include low blood counts, frequent infections, the development of a more aggressive form of cancer (non-Hodgkin lymphoma , also called large B-cell lymphoma , or Hodgkin lymphoma), an increased risk of other cancers, a progression to other leukemias (prolymphocytic leukemia, acute lymphocytic leukemia , or acute myeloid leukemia , and immune system disorders (autoimmune hemolytic anemia).

If you experience any persistent signs and symptoms of chronic lymphocytic lymphoma such as weakness, fatigue, enlarged, painless lymph nodes around the neck, under the arm (axillary), or in the stomach or groin, a feeling of pain or fullness below the ribs, unexplained weight loss, fever, chills, frequent colds, recurrent infections, easy bruising or bleeding, bleeding gums, nosebleeds, flat, pinpoint, red spots under the skin (petechiae), shortness of breath (dyspnea), night sweats, pneumonia, or anemia, contact your doctor as soon as possible. If a diagnosis of chronic lymphocytic leukemia is confirmed, you will also be referred to leukemia and cancer specialists known as hematologists and oncologists.

While there is no known method of preventing chronic lymphocytic leukemia, if an individual’s white blood cell count is found to extremely high, follow-up tests may be ordered. Chronic lymphocytic leukemia that is found early and followed with observation may have a better overall outcome (prognosis); therefore, if you experience any of the above symptoms, it is important to see your doctor as soon as possible for testing.